The process of cell-cell adhesion plays a central role in the development of metazoan organisms. Our present knowledge of these interactions, however, does not include a description of the molecules or mechanisms involved in the formation of cell-cell bonds. The goal of our studies is to characterize in detail the structures of cell surface polypeptides that have been demonstrated to be involved in adhesion among cells of the chick embryo. Our studies will focus on N-CAM, the glycoprotein found on the surfaces of neuronal cells whose function is required in the adhesion of neuronal cells of each other and is associated with a variety of important events in the formation of nerve tissue. The studies will be aimed at describing the organization of subunits, locating prosthetic groups, identifying functional and antigenic regions, describing the chemical composition and determining the amino acid sequence of N-CAM. Similar studies will be carried out on L-CAM, a cell-surface protein that is involved in the calcium-dependent aggregation of liver cells, and CD-CAM, a cell surface protein that is distinct from N-CAM and L-CAM and is involved in the calcium-dependent aggregation of neuronal cells. In addition, we will use monoclonal antibodies to identify these cell adhesion molecules in other species, particularly the mouse, and to identify embryonic antigens with unmusual distributions indicating that they may also be involved in the assembly of tissue patterns. The techniques to be used for these studies have been developed in our preliminary studies of these proteins and in our work over the last 15 years on the structures of immunoglobulins, lectins, histocompatibility antigens, and Beta2-microglobulins. The detailed description of cell adhesion molecules should provide the necessary basis for defining precise mechsnisms by which these molecules contribute to the making and breaking of cell-cell contracts. Such a description will also help clarify their role in embryogenesis. A definition of adhesive mechanisms at this fundamental level will substantially increase our knowledge of their role in embryonic development and could have important consequences for understanding the origins of many birth defects.